Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases

Wang, Bin; Zeng, Hongtao; Liu, Jingliu; Sun, Miao

doi:10.3389/fnins.2021.755554

Cited by 44 publications

(22 citation statements)

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“…For example, Vázquez-Borsetti et al (2016) reported that a 20-min hypoxia-ischemia insult on perinatal rats led to social deficits and loss of neurons. However, hypoxia studies on prenatal and perinatal rodents often apply artery ligation to induce hypoxia-ischemia exposure ( Wang et al, 2021a ), which is much harsher than the hypoxia treatment in our study. Driscoll et al (2018) showed that 10% oxygen applied on pregnant Sprague-Dawley rats transiently for 3, 5, or 7 min combined with ligation of the infra-renal abdominal aorta and uterine arteries caused social deficits and inflammation in postcesarean pups at postnatal day 30.…”

Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation

Zhang

Yang

et al. 2023

Front. Mol. Neurosci.

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IntroductionHypoxia is an environmental risk factor for many disorders throughout life. Perinatal hypoxia contributes to autism spectrum disorder (ASD), while hypoxic conditions in the elderly facilitate memory deficits. However, the effects of hypoxia on adolescence remains elusive. CNTNAP2 is a critical molecule in ASD pathogenesis with undefined mechanisms. We investigate hypoxia’s impact on adolescence and the underlying mechanism related to CNTNAP2.MethodsThree-chamber social approach test, Y maze, Morris Water Maze and Open Field Test were applied to evaluate behavioral alterations. Immunoblotting, 5′- RACE and dual-luciferase reporter assay were performed to examine CNTNAP2 protein expression, transcription start site (TSS) of human CNTNAP2 gene and CNTNAP2 promoter activity, respectively.ResultsIntermittent hypoxia treatment improved social behaviors and working memory in adolescent mice. CNTNAP2 was increased in the brains of hypoxia-treated mice. The sequencing results identified the TSS at 518 bp upstream of the translation start site ATG. Hypoxia upregulated CNTNAP2 by interacting with functional hypoxia response elements in CNTNAP2 promoter.ConclusionIntermittent hypoxia enhanced sociability and working memory associated with CNTNAP2 upregulation. Our study provides novel insights into intermittent hypoxia’s impact on development and the interaction between genetic and environmental risk factors in ASD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation

Zhang

Yang

et al. 2023

Front. Mol. Neurosci.

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“…Hypoxia has been associated with other psychiatric disorders including schizophrenia and other non‐affective psychoses (Zornberg et al, 2000), but the exact mechanisms underlying this phenomenon are not clear. Altered epigenetic programming, endocrine axis dysfunction, and oxidative damage are hypothesized to be underlying mechanisms linking prenatal hypoxia with abnormal brain development and plasticity (reviewed in Wang et al, 2021). Thus, we cannot exclude that the link between low Apgar and offspring AN is hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Exposures during pregnancy and at birth are associated with the risk of offspring eating disorders

Ozsvar,

Gissler,

Lavebratt

et al. 2023

Intl J Eating Disorders

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BackgroundEating disorders (ED) are severe psychiatric disorders, commonly debuting early. Aberrances in the intrauterine environment and at birth have been associated with risk of ED. Here, we explore if, and at what effect size, a variety of such exposures associate with offspring ED, that is, anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS).MethodsThis population‐based cohort study, conducted from September 2021 to August 2023, used Finnish national registries of all live births in 1996–2014 (N = 1,097,753). Cox proportional hazards modeling was used to compare ED risk in exposed versus unexposed offspring, adjusting for potential confounders and performing sex‐stratified analyses.ResultsA total of 6614 offspring were diagnosed with an ED; 3668 AN, 666 BN, and 4248 EDNOS. Lower risk of offspring AN was seen with young mothers, continued smoking, and instrumental delivery, while higher risk was seen with older mothers, inflammatory disorders, prematurity, small for gestational age, and low Apgar. Offspring risk of BN was higher with continued smoking and prematurity, while lower with postmature birth. Offspring risk of EDNOS was lower with instrumental delivery, higher for older mothers, polycystic ovary syndrome, insulin‐treated pregestational diabetes, antibacterial treatment, prematurity, and small for gestational age. Sex‐specific associations were found.ConclusionsSeveral prenatal and at birth exposures are associated with offspring ED; however, we cannot exclude confounding by maternal BMI. Nevertheless, several exposures selectively associate with risk of either AN, BN, or EDNOS, and some are sex‐specific, emphasizing the importance of subtype‐ and sex‐stratified analyses of ED.Public SignificanceWe define environmental factors involved in the development of different ED, of importance as preventive measure, but also in order to aid in defining the molecular pathways involved and thus in the longer perspective contribute to the development of pharmacological treatment of ED.

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“…Emergency cesarean delivery is a composite outcome of abnormalities in pregnancy with one or more serious adverse events in the mother and/or fetus, such as pre-eclampsia, placenta previa, and fetal distress. 18 These adverse events may have deleterious effects on the development of the fetal central nervous system, 19 which may lead to infantile esotropia. Further research is needed to investigate the association between different adverse events and infantile esotropia.…”

Section: Discussionmentioning

confidence: 99%

Association between Gestational Age, Birth Weight, Parental Age at Childbirth, Mode of Delivery, and Infantile Esotropia

et al. 2022

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SIGNIFICANCE:This study investigated the potential perinatal risk factors associated with infantile esotropia in a Chinese population, including advanced parental age at childbirth and mode of delivery. The findings may be significant in developing better intervention strategies for infantile esotropia.PURPOSE: This study aimed to investigate the associations between gestational age, birth weight, parental age at childbirth, mode of delivery, family history of strabismus, and infantile esotropia in the Chinese population.METHODS: Ninety-nine patients with infantile esotropia and 117 control subjects were enrolled between March 2018 and March 2021. Detailed questionnaires were administered to parents to collect relevant information. Univariate and multivariate logistic regression models were used to identify possible risk factors of infantile esotropia. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS:Infantile esotropia was associated with low birth weight (<2500 g; OR, 4.235; 95% CI, 1.460 to 12.287; P = .008) and emergency cesarean delivery (OR, 2.230; 95% CI, 1.127 to 4.413; P = .02). CONCLUSIONS:The findings suggest that low birth weight and emergency cesarean deliveries are risk factors for infantile esotropia, highlighting a need for collaborative care between obstetricians, pediatricians, and vision care providers.

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Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases

Cited by 44 publications

References 122 publications

Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation

Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation

Exposures during pregnancy and at birth are associated with the risk of offspring eating disorders

Association between Gestational Age, Birth Weight, Parental Age at Childbirth, Mode of Delivery, and Infantile Esotropia

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